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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although neuroanatomical and neurophysiological features of neurons in the ferret trachea have been studied, the neural mediators associated with this plexus have not been completely characterized. The purpose of this study was to examine the occurrence of choline acetyltransferase (ChAT), nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), and substance P(SP) in the intrinsic neurons of this plexus. The distribution of double- and triple-labeled neurons was quantified in cryostat sections and in whole mounted specimens to evaluate the neurochemical profiles. About 85% of the nerve cell bodies with ChAT immunoreactivity (ChAT-IR) were located in ganglia of the longitudinal trunks or the closely associated bridge ganglia. Approximately 15% of ChAT-positive neurons were in ganglia of the superficial muscular plexus. Conversely, VIP-IR neurons were most frequent in the superficial muscular plexus (>75%) and, <10% were observed in the longitudinal trunks or bridge neurons. Most NOS- and SP-IR neurons were also located in the superficial muscular plexus. The following distribution of neurochemical profiles was determined for neurons of the superficial muscular plexus: 11% only NOS, 20% only VIP, 5% only SP, 67% NOS and VIP, and 40% VIP and SP. NOS, VIP, and SP were frequently localized in the same nerve cell body. The occurrence of nerve terminals containing only SP located around the borders of individual NOS/VIP/SP-containing neurons suggests possible sensory innervation to the airway neurons. The results demonstrate that: (1) most cholinergic nerves do not contain VIP, NOS, or SP; (2) cholinergic neurons are predominantly located in the longitudinal trunk ganglia; (3) VIP, NOS, and SP are predominantly located in the superficial muscular plexus ganglia; and (4) nerve terminals containing exclusively SP, suggesting possible sensory origin, are closely associated with some neurons in the plexus.
Am J Respir Cell Mol Biol 1996 Mar
PMID:Neurochemical characterization of intrinsic neurons in ferret tracheal plexus. 884 70

The predicted C-terminal dodecapeptide of the human vesicular acetylcholine transporter (VAChT), deduced from the unique open reading frame of the recently cloned human VAChT cDNA, was conjugated through an N-terminal cysteine to keyhole limpet hemocyanin and used as an immunogen to generate polyclonal antihuman VAChT antibodies in rabbits. The distribution of the VAChT antigen in representative regions of the cholinergic nervous system was examined and compared to that of the acetylcholine biosynthetic enzyme choline acetyltransferase (ChAT), a specific marker for cholinergic neurons. VAChT immunoreactivity was localized in cell bodies of neurons in the basal forebrain and ventral horn of the spinal cord, regions in which major cholinergic projection systems to the cerebral cortex and to skeletal muscle, respectively, originate. The primate caudate nucleus contained numerous VAChT-positive interneurons. VAChT immunoreactivity was visualized in both cell bodies and extensive terminals in striatal interneurons, in contrast to formalin-fixed, deparaffinized sections stained for ChAT, in which cell bodies and fibers were stained but nerve terminals were less well visualized than with the VAChT antiserum. VAChT-positive nerve fibers were visualized in routinely immersion-fixed, paraffin-embedded human cerebral cortex, comparable to the density of fibers observed in perfusion-fixed Bouin's-postfixed monkey cerebral cortex. Extensive investment of virtually all principal ganglion cells of thoracic sympathetic ganglia of monkey and human with VAChT-positive nerve terminals was observed. VAChT-positive cell bodies, presumably corresponding to cholinergic sympathetic sudomotor neurons, were a significant fraction of the total principal cell population in monkey and human thoracic sympathetic ganglia.
J Mol Neurosci 1995
PMID:Human and monkey cholinergic neurons visualized in paraffin-embedded tissues by immunoreactivity for VAChT, the vesicular acetylcholine transporter. 886 Feb 34

Apolipoprotein-E-deficient mice provide a useful model system for studying the role of apolipoprotein E (apoE) in brain function. In the present study, we characterized the cholinergic function of these mice and the extent of phosphorylation of their cytoskeletal protein tau. Morris water maze tasks revealed deficits in working memory that were accompanied by a specific decrease in hippocampal and cortical choline acetyltransferase activities. Immunoblot experiments utilizing native and dephosphorylated tau and antibodies directed against specific phosphorylated and unphosphorylated tau epitopes revealed that tau of the apoE-deficient mice is hyperphosphorylated. These results show that apoE-deficient mice have cognitive cholinergic and cytoskeletal derangements and point out the importance of this model for studying the role of apoE in neuronal function.
Mol Chem Neuropathol
PMID:Biochemical and cognitive studies of apolipoprotein-E-deficient mice. 887 47

We report here the behavioral and biochemical recovery induced by the nerve growth factor (NGF) administration in AF64A-treated rats. Retention in the passive avoidance test was affected by lesion but it was significantly improved after the NGF treatment. Similar results were observed in the performance during the Morris water maze (MWM) task. Remarkable losses in the ChAT activity were detected in some brain regions from lesioned rats. The NGF-induced alleviation of choline acetyltransferase (ChAT) activity losses and cognitive functions suggest a trophic and protective action on the remaining cholinergic neurons after the lesion. Thus NGF therapy could be considered as a possibility mainly in the early course of Alzheimer disease.
Mol Chem Neuropathol
PMID:Effects of chronic infusion of nerve growth factor (NGF) in AF64A-lesioned rats. 887 56

Transcription factor, cAMP response element-binding protein (CREB), which is phosphorylated by cAMP-dependent kinase via an increase in cAMP, and regulates gene transcription by binding to the cAMP response element (CRE) on target genes. We examined age-dependent alterations in the DNA-binding activity of CREB in rat brain regions, and the effects of rolipram, a cAMP-specific phosphodiesterase (PDE) inhibitor on the CRE-binding activity by electrophoretic mobility-shift assay (EMSA). A marked age-dependent decrease in the CRE-binding activity was shown in all brain regions examined, especially in the basal forebrain, the striatum and the hippocampus. Furthermore, CRE-binding activities in the basal forebrain of both young-adult and aged rats significantly increased 2 h after rolipram administration (1 mg/kg, i.p.), and the rolipram treatment recovered the decreased CRE-binding activity in the aged rats. The saturation experiment in EMSA also revealed that rolipram reversed the decrease in the maximum CRE-bindings in the basal forebrain with aging. Since the 5' upstream region of the rat choline acetyltransferase (ChAT) gene contains CRE, and ChAT-positive neurons in the basal forebrain project to the frontal cortex and the hippocampus, rolipram may exert its previously reported ameliorating effect on the age-related reductions of ChAT activities in the frontal cortex and the hippocampus by phosphorylating CREB in the basal forebrain with activation of cAMP-dependent protein kinase via inhibition of PDE.
Brain Res Mol Brain Res 1996 Sep 05
PMID:Alterations of cAMP response element-binding activity in the aged rat brain in response to administration of rolipram, a cAMP-specific phosphodiesterase inhibitor. 888 54

NMDA receptors are composed of proteins from two families: NMDAR1, which are required for channel activity, and NMDAR2, which modulate properties of the channels. The mRNA encoding the NMDAR2D subunit has a highly restricted pattern of expression: in the forebrain, it is found in only a small subset of cortical, neostriatal and hippocampal neurons. We have used a quantitative double-label in situ hybridization method to examine the expression of NMDAR2D mRNA in neurochemically defined populations of neurons. In the neostriatum, NMDAR2D was expressed by the interneuron populations marked by preprosomatostatin (SOM), the 67-kDa form of glutamic acid decarboxylase (GAD67), parvalbumin (PARV), and choline acetyltransferase (ChAT) mRNAs but not by the projection neurons expressing beta-preprotachykinin (SP) or preproenkephalin (ENK) mRNAs. In the neocortex, NMDAR2D expression was observed in only a small number of neurons, but these included almost all of the SOM-, GAD67-, and PARV-expressing interneurons. In the hippocampus, NMDAR2D was not present in pyramidal or granule cells, but was abundant in SOM-, GAD67-, and PARV-positive interneurons. NMDAR2D expression appears to be a property shared by interneurons in several regions of the brain. The unique electrophysiological characteristics conveyed by this subunit, which include resistance to blockade by magnesium ion and long channel offset latencies, may be important for the integrative functions of these neurons. NMDAR2D-containing receptor complexes may prove to be important therapeutic targets in human disorders of movement. In addition, the presence of NMDAR2D subunits may contribute to the differential vulnerability of interneurons to excitotoxic injury.
Brain Res Mol Brain Res 1996 Nov
PMID:Expression of NMDAR2D glutamate receptor subunit mRNA in neurochemically identified interneurons in the rat neostriatum, neocortex and hippocampus. 891 84

The objective was to replicate a reported decrease of choline acetyltransferase (ChAT) in the mesopontine tegmentum of deceased schizophrenics and to see if such a decrease is related to their cognitive status as measured during life. Rigorous antemortem psychiatric evaluations were performed on our large population of schizophrenic patients. Mesopontine tissue was collected promptly following death from eight of these patients, from an additional five schizophrenics without systematic premortem psychiatric evaluation, and from control subjects. ChAT content of this brain tissue was determined using Western immunoblot analysis. There were 13 schizophrenic patients and 8 control subjects. The mean age of subjects in the two groups was similar (64 +/- 9 yr vs 63 +/- 10 yr). Even in the face of reduced post mortem intervals in the patients with schizophrenia, mesopontine tegmental ChAT concentrations were depressed by 70% in schizophrenic patients (1.28 +/- 1.74 vs 4.39 +/- 3.20 ng ChAT/micrograms tissue protein, P < 0.01), and correlated with orientation and reasoning (rs = 0.90 and 0.98, respectively) in those subjects assessed antemortem. Mesopontine ChAT concentrations are depressed in schizophrenia and correlate significantly with measures of cognitive performance in patients with this disorder.
Mol Chem Neuropathol
PMID:Decreased mesopontine choline acetyltransferase levels in schizophrenia. Correlations with cognitive functions. 897 95

The organization and distribution of the mRNA for the putative vesicular transporter for acetylcholine (VAChT) was studied in the rat brain by use of digoxigenin-labeled riboprobes and in situ hybridization technology. Signal was observed in all neural regions deduced to contain cholinergic somata on the basis of previous histochemical investigations employing choline acetyltransferase riboprobes and prior immunocytochemical studies with antibodies against choline acetyltransferase. It was absent in areas believed to contain no cholinergic neurons. Anti-sense riboprobes hybridized to the mRNA for the putative VAChT: (a) the projection neurons of the various nuclei of the basal nuclear complex, (b) the local circuit cells of the dorsal and ventral striata, (c) the projection neurons of the mesopontine complex, (d) perikarya in the ventral 2/3 of the medial habenula, (e) the somatic motor and autonomic cells of cranial nerves 3-7 and 9-12, as well as perikarya in the dorsal and ventral cochlear nuclei presumably giving rise to efferent fibers of cranial nerve 8, and (f) the alpha-motor and gamma-efferent motor neurons of the spinal cord. In addition, the mRNA for the VAChT was found in a few somata, probably ectopically located cells of the basal nuclear complex, in the internal capsule, central nucleus of the amygdala, entopeduncular nucleus, and zona incerta. It was also detected in some cell bodies in the reticular part of the substantia nigra, probably the rostral extension of the mesopontine complex, in the parabigeminal nucleus, and around the central canal in the spinal cord but not in cortical, hippocampal, and cerebellar perikarya. It is concluded that, like choline acetyltransferase, the mRNA for the putative acetylcholine vesicular transporter is another specific marker for neurons utilizing acetylcholine as a neurotransmitter. Further investigations of that transporter could have important implications for various diseases involving cholinergic systems, such as Alzheimer's disease.
Brain Res Mol Brain Res 1996 Dec 31
PMID:Differential distribution of the putative vesicular transporter for acetylcholine in the rat central nervous system. 903 20

Choline acetyltransferase (ChAT, EC 2.3.1.6) is the biosynthetic enzyme for acetylcholine. We have previously shown that multiple ChAT mRNA species with different 5'-noncoding regions are expressed in the rat and mouse. However, the diversity of ChAT mRNA species in human has not completely been elucidated. In this work N1- and N2-type ChAT cDNAs were cloned from a human brain cDNA library and the N-exon located in the human ChAT gene. Polymerase chain reaction analysis indicates that four species of ChAT mRNAs (R-, N1-, N2- and M-types) are produced in human brain and spinal cord. In all human transcripts, the ATG initiation codon in the rat, mouse and pig was replaced by ACG, which does not serve as an initiation codon for translation. In vitro translation and mammalian expression analyses revealed that N1-, N2- and R-type mRNAs give rise to a single 69 kDa enzyme, while M-type mRNA produces both 82 and 69 kDa enzymes. The translation efficiency of M-type mRNA was lower than that of the other mRNA species. Moreover, the translation efficiency of human ChAT mRNAs was considerably lower than that of rat ChAT mRNA, suggesting that the ATG codons for human ChAT are unfavorable for translation initiation compared with the initiation codon for rat ChAT. These results provide rational explanations for the previous reports that human ChAT protein purified from the brain and placenta had 66-70 kDa molecular mass, and that ChAT activity in a single motor neuron of human was far lower than that of other vertebrates. Sequencing of monkey ChAT gene showed that the initiation ATG in rodent ChAT was also replaced by ACA in the monkey.
Brain Res Mol Brain Res 1997 Mar
PMID:Human choline acetyltransferase mRNAs with different 5'-region produce a 69-kDa major translation product. 907 74

Moderate lesions of the septohippocampal pathway by intraventricular infusions of ethylcholine aziridinium (AF64A) induced a dose-dependent decrease of hippocampal choline acetyltransferase (ChAT) activity, which partially recovered between 1 and 5 weeks after treatment. The cholinergic deficit was associated with an increase in nerve growth factor (NGF) mRNA only within the hippocampal dentate gyrus and hilus by maximally 51% and 111% 3 and 7 weeks after AF64A treatment, respectively, whereas no changes in brain-derived neurotrophic factor- and neurotrophin-3 mRNA were observed. The content of NGF protein transiently increased in the ventral part of the hippocampus 3 weeks after AF64A infusion but returned to control levels at 5 weeks. At that time, however, NGF content as well as ChAT activity were significantly increased in the septum, suggesting an increased utilization of NGF by the remaining cholinergic neurons. Thus, the present data provide correlative evidence for a critical role of endogenous NGF in neuroregeneration and plasticity of the cholinergic basal forebrain in case of incipient damage.
Brain Res Mol Brain Res 1997 Apr
PMID:Moderate lesion of the rat cholinergic septohippocampal pathway increases hippocampal nerve growth factor synthesis: evidence for long-term compensatory changes? 910 89


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